Most of the biochemical studies on the characterization of erythroid cells, which require a mass number of cells, were and still are performed using cell lines as a model. This is exemplified by the studies on the regulation of globin gene expression that have highly relied on the use of the murine MEL cells and the human K562, HEL, and UT-7 cell lines (G. Stamatoyannopoulos, et al., The Molecular Basis of Blood Diseases, 135 (2001)) of primary cells, as many regulatory pathways have been altered during the transformation process that led to their immortalization. Therefore, investigators have tried to establish in vitro unilineage differentiation of primary erythroid cells to be used as a model in those studies (V. Glaser, Nat. Biotechnol. 16, 709 (1998)). Homogeneous populations of primary human erythroid cells through unilineage-specific culture conditions have relied on the use of progenitor (CD34+) cells purified from neonatal blood or from adult marrow and cultured in the presence of stimulators of the glucocorticoid receptor, such as dexamethasone (B. Panzenbock, et al. Blood 92, 3658-3668 (1998); M. von Lindern, et al. Blood 94, 550-559 (1999)). This method allows up to one-thousand-fold amplification of differentiated cells. However, for practical and ethical reasons, it is not always possible to obtain specimens with a number of cells sufficient for CD34+ selection from a specific donor. Conversely, it is well known that the behavior in culture of primary cells reflects the genomic heterogeneity of the donor from whom they are derived (C. T. Jordan et al., Curr. Opin. Cell Biol. 10, 716-720). There are many cases in which unilineage differentiation from a specific donor would allow an estimate of the influence of a particular genetic background on the response being studied. In these cases, it may not be ethically appropriate to harvest marrow or blood from the patient in amounts sufficient for CD34+ cell purification. Unilineage differentiation of erythroid cells has been achieved, starting with light-density cells purified from the blood with a two-step culture method that physically separates the stimulation of the cells with growth factors, allowing commitment with those required for the maturation of erythroid cells (E. Fibach et al., Blood 73, 100 (1989)). However, the amplification obtained with such a technique is very modest and does not allow mass cell production. Herein is a description of a new two-phase culture method that allows mass production of primary human erythroid cells, starting from the light-density cells of normal donors and thalassemic patients. In both cases, highly homogeneous primary erythroid cells are produced in numbers sufficient for biochemical and molecular studies from very modest volumes (10 mL) of blood. Therefore, this method will be useful for donorspecific studies of hemoglobin F reactivation, to identify inducers targeted for each specific patient.